The overall objective of this project is to study the decreased ability of mitochondria from aged animals to synthesize proteins and how this relates to heme synthesis, heme concentration and cytoplasmic protein synthesis. Livers will be obtained from animals varying in age from 1-2 weeks to 2-3 years and compared as to their ability to synthesize mitochondrial proteins; cytoplasmic proteins; and heme; as well as the activity of the heme synthetic enzymes (particularly delta-aminolevulinic acid synthetase), the total cellular and sub-cellular heme concentrations; and for the presence of the hemin controlled repressor. Three systems will be utilized from the liver in these studies; an isolated mitochondrial protein synthesizing system, a dispersed liver cell system and in vivo labelling system. By studying and comparing the results from animals of varying ages it may be possible to test the hypothesis that the decrease in mitochondrial protein synthesis seen with age in the initial and primary lesion responsible for a decrease in delta-aminolevulinic acid synthetase activity resulting in decreased heme synthesis, heme concentration, activation of the hemin controlled repressor and finally a decrease in cytoplasmic protein synthesis. An alternative hypothesis, also testable, is that the decrease in cytoplasmic protein synthesis in age is the primary lesion resulting in a build-up of free heme which will then inhibit mitochondrial protein synthesis with a subsequent decrease in heme synthesis.